The objective is to determine the efficacy of hyperthermia in the treatment of human malignancies when combined with surgery, radiation or chemotherapy. The research involves a multidisciplinary effort, including biological, physical, and clinical scientists. Specific aims of the biological projects within this program are designed to further describe the underlying biochemical and molecular principles of cellular damage by hyperthermia which leads to cytotoxicity. The biological projects are designed to test basic concepts which have potential clinical applications. The physics and engineering project has the overall goal of delivering desired therapeutic temperatures to any anatomical site in a human cancer patient, to document the delivered dose, and to insure patient safety during treatment. A major subtheme integrates the various basic science and clinical projects, and is the development of thermal dosimetry. This subtheme impacts all projects and attempts to, first, relate time and temperature parameters in a single function and, second, document these parameters in patients undergoing hyperthermia therapy such that clinical responses can be correlated with thermal dose. The human clinical trials component of this program has been designed to ascertain the efficacy of hyperthermia, either localized, regional or systemic, combined with radiation or chemotherapeutic drugs in the treatment of specific malignancies. The major aim of the clinical project is to conduct site-specific randomized or phase I/II clinical trials. These trials have been designed with the long term goal of developing potentially curative therapies for these diseases. Two major classes of trials are proposed, one investigating the combination of hyperthermia and radiotherapy and the other studying combinations of hyperthermia and chemotherapy. Diseases in the former group of trials include stages B2 and C bladder cancer and advanced (stages III and IV) head and neck cancers. The latter group of trials will focus on advanced, recurrent ovarian cancers. Thus, this Program is designed to investigate the basic biological and physical principles of hyperthermia, in a comprehensive manner and then to determine the usefulness of this modality in combination with radiation and drugs in cancer therapy.